The effects of L-deprenyl treatment, alone and combined with GM1 ganglioside, on striatal dopamine content and substantia nigra pars compacta neurons.
The present study examined the effects of GM1 ganglioside and the monoamine oxidase B (MAO-B) inhibitor L-deprenyl, alone and in combination, on striatal dopamine (DA) and DOPAC levels, and the density of tyrosine hydroxylase (TH) positive neurons in the substantia nigra pars compacta (SNc) of C57bl/6J mice following MPTP administration (20 mg/kg, s.c., twice daily for 5 days). GM1 treatment (30 mg/kg, i.p., daily for 3 weeks, beginning 24 h after the last MPTP injection) partially restored striatal DA levels and rescued SNc neurons. A high dose of L-deprenyl, inhibiting MAO-B activity, (10 mg/kg, i.p. every other day for 3 weeks beginning 3 days after the last MPTP injection) increased striatal DA content, but did not rescue TH-positive SNc neurons. A low dose of L-deprenyl (0.01 mg/kg, i.p. every other day for 3 weeks beginning 3 days after the last MPTP injection) had no effect on either striatal neurochemistry or the rescue of SNc TH-positive neurons. Co-administration of GM1 and high dose L-deprenyl caused a synergistic increase in striatal DA levels, above that obtained with either GM1 or high dose L-deprenyl alone. Co-administration of GM1 and low dose L-deprenyl was not only not synergistic, but caused GM1s effects to be antagonized. The results do not confirm previous findings that low dose L-deprenyl administration in vivo after MPTP can rescue SNc neurons. Given GM1's potential as an adjunct to present anti-parkinsonian medications which include L-deprenyl, it will be important to further investigate the interactions between these two potential therapies.
Rothblat
D S
DS
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Schneider
J S
JS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D005677:G(M1) Ganglioside; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine